One of our approaches to neurobiology is to study perturbations in synaptic function or development caused by single gene mutations. In much the same way as previously done for biosynthetic pathways in microorganisms, specific components of neural activity or steps in neural development may be studied by altering specific genes. Neuromuscular junctions in Drosophila larvae are very accessible to neurophysiology, because the preparation is thin and visible with Normarski optics, and the nerve terminals are readily accessible to experimental manipulations. The quantal nature of transmitter release, the ionic basis of the membrane resting potential and the excitatory junctional potential, as well as postsynaptic action of L-glutamate, have been worked out in detail. Since single-gene mutations affecting the synapse can be isolated, one can combine genetics, electrophysiology and biochemistry in studying the synapse. So far three mutations affecting neuromuscular transmission have been found, mapped genetically and studied electrophysiologically. In addition, several mutations in the bithorax gene complex, studied extensively by Dr. E. B. Lewis at Caltech, were found to produce specific changes in the larval muscle pattern. More mutations affecting the synapse will be studied with the hope of revealing hitherto unsuspected processes underlying synapse formation or changes of synaptic efficacy.